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Electric fields deliver drugs into tumors

Chemotherapy has been a mainstay of cancer treatment for decades. But most of these drugs are toxic to healthy cells, and others have a hard time penetrating tumors. Now researchers report that they’ve come up with a potential solution for both problems. They used electric fields to drive chemo compounds specifically into difficult-to-treat tumors in animals, dramatically increasing the drugs’ concentration within the tumor and shrinking it.

Like all potential cancer treatments from animal studies, the approach has a long way to go before it reaches patients. However, the strategy is encouraging, says Robert Langer, a chemical engineer at the Massachusetts Institute of Technology in Cambridge and an expert in drug delivery, who wasn’t involved with the work. “The initial data look quite promising.”

Joseph DeSimone, a chemist at the University of North Carolina, Chapel Hill, who headed up the new study, says he became interested in working on hard-to-treat tumors after years of developing novel approaches to deliver drugs orally. He also recently lost a close colleague to pancreatic cancer, who like other patients with the disease was ravaged by the side effects of chemo.

DeSimone was familiar with a different approach for delivering chemo drugs locally into tumors that involves putting them in biodegradable polymers that slowly decay after being implanted next to a tumor, releasing a steady supply of the drug. But that approach hasn’t worked well with pancreatic cancer. Like some other tumors, pancreatic tumors build up a high internal fluid pressure, which pushes against medicines trying to diffuse in and prevents them from concentrating deep within the cancerous tissue.

In the last few years, other research groups had shown that it was possible to use small electric fields to drive medicines into the eye and bladder. DeSimone and his colleagues wanted to see if they could use the same strategy to drive chemotherapeutic drugs into solid tumors. To do so, they built a setup with a small reservoir designed to hold a liquid chemotherapy drug. This reservoir also contained one of two electrodes that create the electric field needed to drive the drug into nearby tumor tissue. In one setup, which was designed to deliver chemotherapy drugs to tumors deep within the body, the researchers implanted the reservoir and its electrode on one side of a tumor, while they implanted the counterelectrode on the tumor’s opposite side. In the other setup, which was designed to treat tumors just under the skin, the reservoir containing one electrode was placed on the skin just above the tumor in mice, while the second electrode was placed on the skin on the opposite side of the animal’s body. So in the latter case, the electric field generated between the two electrodes pushed the drugs through the skin into the tumor below.

DeSimone and colleagues tested their drug delivery method on mice with pancreatic or breast cancer. They also implanted their devices on the surface of the pancreas of dogs without tumors, in an effort to better gauge the flow of drugs into tissues of larger animals such as humans. In all the studies, the devices required low electric currents and voltages, below the pain register in the animals, to drive the drugs into the tumors. The approach works, DeSimone explains, because many liquid drug molecules are “polar,” which causes them to move in an electric field toward an electrode with an opposite charge from the nearby electrode where they start.

The team got several promising results. In one experiment, the researchers started with mice that had been implanted with human pancreatic cancer tumors. One group of mice was then implanted with the electrode setup and administered an anticancer drug called gemcitabine twice a week for 7 weeks. Control animals received either saline through the same electrode setup or intravenous (IV) doses of saline or gemcitabine. The researchers report online today in Science Translational Medicine that the animals in the experimental group had far higher gemcitabine concentrations in their tumors compared with mice that received the IV drug. That caused the tumors to shrink dramatically in the experimental animals, whereas tumors in mice that received IV gemcitabine or saline continued to grow.

In a separate set of experiments, DeSimone and his colleagues delivered the anticancer drug cisplatin through the skin of mice that had either of two different types of aggressive breast cancer implanted just below the skin. They found that the local delivery of the drug strongly inhibited tumor growth and doubled the survival time of the mice. In a final study on dogs, the researchers found that electric delivery of gemcitabine through the implanted device increased the concentration of the drug sevenfold within pancreatic tissue but reduced it 25-fold in the bloodstream, compared with animals that received the drug through IVs.

Taken together, DeSimone argues that the new drug delivery strategy holds out hope for increasing the effectiveness of chemotherapy and reducing its side effects. That would be particularly welcome, he says, when it comes to battling tumors, such as pancreatic cancer, that wrap themselves around other organs and major blood vessels, making them difficult to remove surgically. Even if the treatment doesn’t make tumors disappear completely, it could shrink them enough to make more people candidates for surgery, he says.

But just how these devices might work in people isn’t yet clear. In the current studies, tiny tubes connected to the implanted devices continually replenish chemo drugs pumped into the animals. Whether that setup would work best in people, or whether larger reservoirs of the drugs could be implanted, remains to be seen.